Cytokines induced by long-term potentiation (LTP) recording: a potential explanation for the lack of correspondence between learning/memory performance and LTP.

The relationship between learning/memory performance and long-term potentiation (LTP) induction is ambiguous. Although a large body of data supports a strong correspondence between learning/memory performance and LTP, many studies have also provided evidence to the contrary. In this study, we found that 2-month-old senescence-accelerated mice/prone 8 (SAMP8 mice) displayed both impaired performance in a Morris Water Maze (MWM) and enhanced LTP compared to senescence-accelerated mice/resistance 1 (SAMR1). BALB/c mice challenged with Complete Freund's Adjuvant (CFA) performed better in the shuttle-box test but displayed impaired LTP compared to intact animals. It is interesting that BALB/c mice challenged with Incomplete Freund's Adjuvant (IFA) performed better than intact animals, with no LTP impairment. Cytokine analysis showed no significant differences between the interleukin-6 (IL-6), interleukin-10 (IL-10) or TNF-α content in the intact hippocampal tissues of either the SAMR1 and SAMP8 mice or the immune-challenged BALB/c and intact animals. Further analysis demonstrated that the increase in cytokine content was higher in the hippocampal tissues used for LTP recording in the SAMR1 and CFA-challenged animals compared to the SAMP8 and intact BALB/c mice. A correlation analysis demonstrated that pro-inflammatory cytokines (IL-6 and TNF-α) displayed a negative correlation with LTP, while an anti-inflammatory cytokine (IL-10) displayed a positive correlation with LTP. These results suggest that pro-inflammatory cytokines induced by LTP manipulation in experiments (e.g., via tissue injury caused by electrode insertion) may be one of the factors contributing to the observed lack of correspondence between memory/learning ability and LTP.